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Time
Number
S(t)
I(t)
R(t)
Susceptible
Infected
Recovered
Population
Molecular information provides new ways to combat diseases!
Inference of outbreaks is based on
information about population
Molecular information provides new
ways to combat diseases!
Where are they?
What are they made of?
Why are they so important?
?
?
?
A genome is an organism’s complete
set of chromosomes
Cromosome
Genome
Cell
What is a GENOME?
Cromosome
Genome
Cell
What is a GENOME?
Human cells have
46 chromosomes!
Cromosome
Genome
Cell
A
T
T
A
A
T
G
C
C
G
G
C
C
G
DNA double helix
Base pairs
Cromosome
Genome
Genes
DNA
Genes contain
instructions for
making proteins
Proteins
Proteins perform
many cellular functions
Cell
Each genome contains
ALL
of the information
needed to build and maintain an organism!
The DNA is passed from a
parent to its descendants
Extracellular matrix
Plasma membrane
Chromosome
The bacterial chromosome is
attached to the plasma membrane
at the chromosome‘s
ori
region.
1
The chromosomal DNA replicates.
The attachment points separate as
the cell grows.
2
Fission is complete; two
new cells are formed.
4
The cell begins to divide.
3
From humans to bacteria, all
living organisms have a DNA!
?
?
?
How come bacteria have different DNAs?
DNA replication
The two DNA strands are separated like the two sides of a zipper
A
T
C
G
A
T
A
T
C
G
A
T
C
G
C
G
C
G
A
T
C
G
A
T
C
G
C
A
T
A
T
A
T
C
G
C
C
C
G
G
A
T
A
A
T
A
T
A
T
A
T
C
G
C
G
A
T
A
T
A
T
A
T
C
G
G
T
Free nucleotides
DNA polymerase
Original
DNA
Replication
fork
Chromosome
The enzyme DNA polymerase moves along the exposed DNA strand,
joining newly arrived nucleotides into a new DNA strand
DNA replication
During DNA replication, an
incorrect base may be added
to the growing chain.
DNA replication is very accurate,
but sometimes errors happen!
These changes are called
mutations
Other types of damage to DNA
also cause mutations!
Vancouver
exposure to
radiation
carcinogens
Mutations
ATGCGATCTGCTAGTCAGTCAGTAGTCGTAGT
5
6
7
TACGCTAGACGATCAGTCAGTCATCAGCATCA
CTGCAGTTGAGGACGTAATCTCCAATGCCCATATTAGCGTATCCGAT
1
2
3
4
GACGTCAACTCCTGCATTAGAGGTTACGGGTATAATCGCATAGGCTA
Affect only one chromosome(Inversion)
ATGCGATCTGCTAGTCAGTCAGTAGTCGTAGT
5
6
7
TACGCTAGACGATCAGTCAGTCATCAGCATCA
CTGCAGTTGAGTGGGCATTGGAGATTACGTCTATTAGCGTATCCGAT
1
4
2
GACGTCAACTCACCCGTAACCTCTAATGCAGATAATCGCATAGGCTA
3
Changes in the DNA can affect large pieces of the DNA!
Genes
ATGCGATCTGCTAGTCAGTCAGTAGTCGTAGT
5
6
7
TACGCTAGACGATCAGTCAGTCATCAGCATCA
CTGCAGTTGAGGACGTAATCTCCAATGCCCATATTAGCGTATCCGAT
1
2
3
4
GACGTCAACTCCTGCATTAGAGGTTACGGGTATAATCGCATAGGCTA
Affect only one chromosome(Inversion)
ATGCGATCTGCTAGTCAGTCAGTAGTCGTAGT
5
6
7
TACGCTAGACGATCAGTCAGTCATCAGCATCA
CTGCAGTTGAGTGGGCATTGGAGATTACGTCTATTAGCGTATCCGAT
1
4
2
GACGTCAACTCACCCGTAACCTCTAATGCAGATAATCGCATAGGCTA
3
Genes
Multichromosomal events (Translocation)
modify only the region order
CTGCAGTTGAGGACGTAATCTCCAATGCCCATCTAGTCAGTCAGTAGTCGTAGT
1
2
3
6
7
GACGTCAACTCCTGCATTAGAGGTTACGGGTAGATCAGTCAGTCATCAGCATCA
ATGCGATCTGATTAGCGTATCCGAT
5
TACGCTAGACTAATCGCATAGGCTA
4
Mutations
Overview of some chromosomal translocations involved in different cancers,
as well as implicated in some other conditions, e.g. schizophrenia
Duplication
modify the region order
and the content
Insertion
Deletion
ATGCGATCTGCTAGTCAGTCAGTAGTCGTAGT
5
6
7
TACGCTAGACGATCAGTCAGTCATCAGCATCA
CTGTAATCTCCAGTTGAGGACGTAATCTCCAATGCCCATATTAGCGTATCCGAT
1
2
3
4
2
GACATTAGAGGTCAACTCCTGCATTAGAGGTTACGGGTATAATCGCATAGGCTA
CTGCAGTTGAGGACGTAATCTCCAATGCCCATATTAGCGTATCCGAT
1
2
3
4
GACGTCAACTCCTGCATTAGAGGTTACGGGTATAATCGCATAGGCTA
ATGCGATCTGCTAGTCAGTCAGTAGTCGTAGTGCTAACCA
5
6
7
TACGCTAGACGATCAGTCAGTCATCAGCATCACGATTGGT
8
ATGCGATCTGCTAGTCAGTCAGTAGTCGTAGT
5
6
7
TACGCTAGACGATCAGTCAGTCATCAGCATCA
CTGCAGTTGAGCAATGCCCATATTAGCGTATCCGAT
1
3
4
GACGTCAACTCGTTACGGGTATAATCGCATAGGCTA
Mutations
ATGCGATCTGCTAGTCAGTCAGTAGTCGTAGT
5
6
7
TACGCTAGACGATCAGTCAGTCATCAGCATCA
CTGCAGTTGAGGACGTAATCTCCAATGCCCATATTAGCGTATCCGAT
1
2
3
4
GACGTCAACTCCTGCATTAGAGGTTACGGGTATAATCGCATAGGCTA
Changes in the DNA can affect large pieces of the DNA!
Genes
Cancer
is the most common
human genetic disease
It is caused by mutations occurring
in a number of growth-controlling genes
Sometimes, mutations can harm the organism that carries them...
Sometimes, mutations can be beneficial for the organism that carries them,
but not necessarily good for humans!
We need to update flu vaccines every year, since their genes mutate too fast!
Influenza virus
Sickle cell anemia
is caused by a mutation in the gene that
instructs the building of a protein called hemoglobin
In African populations, having this mutation also
protects against malaria
!
Beneficial?
Mutations are the raw materials of evolution!
lung cancer cell
This particular form of cancer is very lethal, with
a 5-year survival rate of less than 10 percent.
Most cases are caused by smoking
Bat-eared fox (Otocyon megalotis)
Arctic fox (Alopex lagopus)
Adaptations to hot and cold climates
Large ears
: heat exchangers,
passing heat from the fox's blood to the air
Thick fur
: insulation in the
frigid winter
central and southern Africa
The strong, curved beak of the bald
eagle is able to tear the fesh from
large fsh and other sizeable prey.
The curlew uses its long, curved, pointed
beak to extract small crustaceans from
the surface of mud, sand, and soil.
The roseate spoonbill moves
its bill through the water, from
which it flters food items.
Bird beaks are adapted
to specific types of food items
Plants cannot move, but their seeds have adaptations
that allow them to travel varying distances from
the parent plant
The seeds of milkweeds are
surrounded by “kites” of fibers that
carry them on wind currents.
Mammals and birds eat
blackberries, then
disseminate the seeds
when they defecate.
The coconut seed is covered by a
thick husk that protects it as it drifts
across thousands of miles of ocean.
Molecular information provides new
ways to combat diseases!
?
?
?
How can we read DNA?
????????????????????
A single-stranded DNA fragment is isolated
for which the base sequence is to be
determined (the template).
1
Step 1:
Isolate DNA
How to sequence DNA?
Chain termination method!
Step 2:
Create "special" basis
CH
2
H
H
HH
HO
O
O
−
OP
O
O
−
PPO
O
O
−
O
O
O
−
CH
2
H
H
HH
O
O
−
OP
O
O
−
PPO
O
O
−
O
O
O
−
2'
Dideoxyribonucleoside
triphosphate (ddNTP)
3'2'
H
H
H
"Normal" base
(A, T, G, or C)
"Modified" base
(A, T, G, or C)
Absence of OH at 3’ position
means that additional
nucleotides cannot be added.
2
Each special base is
bound to a fluorescent dye.
G
A
T
C
G
A
T
C
Step 3:
Put everything together!
How to sequence DNA?
Chain termination method!
????????????????????
C
G
A
T
C
G
A
T
G
A
T
C
A
T
G
Unknown DNA
Normal basis
Special basis
DNA polymerase
(for DNA replication)
T
C
C
T
A
A
G
A
T
T
A
G
T
T
C
T
G
G
C
T
C
T
C
A
G
G
A
T
T
C
T
A
C
G
Free nucleotides
DNA polymerase stops replication
when a special base is added
The enzyme DNA polymerase moves along the exposed DNA strand,
joining newly arrived nucleotides into a new DNA strand
Step 4:
Let the DNA be replicated
How to sequence DNA? Chain termination method!
C
G
A
T
C
G
A
T
G
A
T
C
Step 5:
Repeat replication
a lot
of times!
How to sequence DNA?
Chain termination method!
Step 6:
Separate and read synthesized fragments
How to sequence DNA? Chain termination method!
Laser
Detector
T
Electrophoresis
Longest fragments
move slower
EJECT
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6
The color at the end of
each fragment is detected
by a laser beam.
How to sequence DNA?
The chain termination method takes too long
when DNA sequences are big...
How to sequence DNA?
Chain termination method!
Genome
Cell
How to sequence DNA? Shotgun sequencing!
The human genome contains
approximately
3 billion
of these base pairs!
DNA is broken up
randomly
into numerous small segments,
which are sequenced using the chain termination method
to obtain
reads
(fragments).
????????????????????
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Nowadays the shotgun sequence is widely
used to sequence all types of genomes...
If you are interested to learn
more about the biological side:
The last two decades have seen a revolution in genome sequencing!
Dramatic increases in speed and efficiency
+ massive reductions in cost
DNA sequencing
... even ours!
DNA sequencing
Sequences always
start at the same point...
Accumulated mutations in the DNA
can help us to combat diseases!
3
How can we use it?
Mutations
Changes in the DNA can affect large pieces of the DNA!
17
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
18
19
20
21
22
23
Anaplastic large cell lymphoma
Burkitt's
lymphoma
CML, ALL
Mantle cell lymphoma
Ewing's sarcoma
Follicular lymphoma
DFSP
Acute promyelocytic leukemia
Acute myelogenous leukemia
CML, ALL
Synovial sarcoma
Schizophrenia
AML
Infertility
Down syndrome
...but they end in
random points
(when special
base is added)
Introduction to genomics for transmission inference
Thanks to Priscila Biller for originally creating
these slides
From genomes to phylogenies
1
Genome
Previous class
Questions
Genome
Human Genome
DNA
Proteins
DNA inherited
DNA bacteria
DNA replication
DNA replication details
Mutations
MutationCauses
Rearrangements-Inversion
Rearrangements-MultipleChromTransl
TranslocationDiseases
DupInDel
MutationHarmCancer
MutFlu
FluVaccine1
FluVaccine2
SickleCellAnemia
MutationsEvolution
BirdBeaks
SeedsAdaptation
HowUseMutations
HowReadDNA
Step1Isolate
Step2SpecialBasis
Step3PutTogether
Step4Replication
Step5Repeat
Step6ReadElectrophoresis
LongRead
ShotgunSequencing
SequencesAvailableCost
BookPurves
A